Cage subsidence causes poor prognoses in patients treated by oblique lumbar interbody fusion (OLIF). Deterioration of the biomechanical environment initially triggers cage subsidence, and patients ...with low bone mineral density (BMD) suffer a higher risk of cage subsidence. However, whether low BMD increases the risk of cage subsidence by deteriorating the local biomechanical environment has not been clearly identified.
OLIF without additional fixation (stand-alone, S-A) and with different additional fixation devices (AFDs), including anterolateral single rod screws (ALSRs) and bilateral pedicle screws (BPSs) fixation, was simulated in the L4-L5 segment of a well-validated finite element model. The biomechanical effects of different BMDs were investigated by adjusting the material properties of bony structures. Biomechanical indicators related to cage subsidence were computed and recorded under different directional moments.
Overall, low BMD triggers stress concentration in surgical segment, the highest equivalent stress can be observed in osteoporosis models under most loading conditions. Compared with the flexion-extension loading condition, this variation tendency was more pronounced under bending and rotation loading conditions. In addition, AFDs obviously reduced the stress concentration on both bony endplates and the OLIF cage, and the maximum stress on ALSRs was evidently higher than that on BPSs under almost all loading conditions.
Stepwise reduction of BMD increases the risk of a poor local biomechanical environment in OLIF patients, and regular anti-osteoporosis therapy should be considered an effective method to biomechanically optimize the prognosis of OLIF patients.
A series of novel quinoline derivatives containing perfluoropropanyl moiety were designed and synthesized. The bioassay results showed that some of them exhibited good control efficacy against ...Pyricularia oryae. The fungicidal activity was affected by the substituted position in the molecule. It was found that the compound 3n possessed highest control effect against P. oryae at different concentration. It is better than that of control Tebufloquin.
Twenty target compounds were designed, synthesized and evaluated in terms of their biological activity.
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Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were ...synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+ bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.
As a kind of pressure-driven membranes, the nanofiltration (NF) membrane and process can separate molecules and ions with different molecular weights and valences, which are well applicable in ...purification, concentration, recovery of resources across various industries. However, in some complex applications, an individual NF membrane often faces the problems of deficient separation efficiency and membrane instability. Researchers have developed NF based hybrid processes, which not only solve the above problems faced by single NF, but also enhance the overall efficiency of hybrid systems involving other separation processes. Currently, there is a notable surge in publications regarding the NF-based hybrid processes, but a systematic review is still lacking. The objective of this review is to provide a comprehensive analysis of the key integration approaches and application areas in which NF-based hybrid process have been utilized in recent years. The challenges awaiting the researcher in the field of NF-based hybrid process are also provided.
•NF-based hybrid process is effective in eliminating NF application bottlenecks.•Systematic analysis of research related to NF-based hybrid processes are performed.•The integration forms and application of NF-based hybrid processes are introduced.•The aims, challenges, and advantages of NF-based hybrid processes are presented.
This paper first elucidates the importance of hydraulic heterogeneity of a rock mass on the design of an underground water‐sealed storage cavern. It then introduces an information fusion approach ...that integrates hydraulic tomography, displacement back analysis, and a stochastic successive linear estimator to map spatially varying hydraulic conductivity (Ks), Young's modulus (E′), cohesion (c′), and internal friction angle (ϕ′). This algorithm yields statistically unbiased estimate of the Ks, E′, c′, and ϕ′ fields and their uncertainty due to insufficient samples of their heterogeneity. Afterward, this uncertainty is translated into the probability of failure distribution around the cavern for the risk assessment. Results show that heterogeneity of Ks plays an important role in the deformation and failure of the cavern. They also show that the proposed approach can reveal more detailed parameter distributions than kriging approach, based on a large number of samples of the parameters before excavations. Further, the predicted probability of failure distribution based on the proposed approach can effectively reflect the actual failure locations.
Key Points
This paper elucidates the importance of hydraulic heterogeneity of a rock mass on the design of underground water‐sealed storage caverns
This paper also proposes fusion approach that integrates HT and displacement back analysis to map spatially varying hydraulic and mechanical properties
The approach identifies the high‐risk instability location around the caverns
Rhizoma Coptidis (Huanglian) is a widely used Traditional Chinese Medicine. However, it causes human as well as animal toxicities. In this study, the results of both in vivo and in vitro experiments ...showed that the toxic constituents in
Rhizoma Coptidis were the alkaloids, mainly berberine.
Rhizoma Coptidis (Huanglian) is a widely used Traditional Chinese Medicine. However, it causes human as well as animal toxicities. In this study, we aimed to ascertain the toxic constituents in
Rhizoma Coptidis.
The acute toxicity of both the total extract and the alkaloid-rich extract of
Rhizoma Coptidis were tested in mice. The dose related tissue concentration of the
Rhizoma Coptidis alkaloids in mice was determined using high performance liquid chromatography with ultraviolet detection. The influence of phenobarbital sodium a non-selective hepatic enzyme (P450) inducer on the acute toxicity of
Rhizoma Coptidis as well as the tissue concentration of the alkaloids was investigated. The cytotoxicity of the
Rhizoma Coptidis alkaloids was tested in six cell lines using the MTT assay.
The median acute oral lethal dose of the total extract of
Rhizoma Coptidis was 2.95
g/kg in mice. The alkaloid-rich extract was much more toxic than the total extract of
Rhizoma Coptidis. Four
Rhizoma Coptidis alkaloids were detected in brain, heart, and lung tissues of mice that received the oral total extract of
Rhizoma Coptidis. Tissue concentration increased nonlinearly with higher doses. Phenobarbital sodium decreased the tissue concentration of every alkaloid as well as the toxicity of
Rhizoma Coptidis. All alkaloids, especially berberine, showed dose and time dependent cytotoxicity.
The toxic constituents of
Rhizoma Coptidis were the alkaloids, mainly berberine.
Avicennia marina (Forsk.) Vierh. is a typical mangrove plant. Its epidermis contains salt glands, which can secrete excess salts onto the leaf surfaces, improving the salt tolerance of the plants. ...However, knowledge on the epidermis-specific transcriptional responses of A. marina to salinity treatment is lacking. Thus, physiological and transcriptomic techniques were applied to unravel the salt tolerance mechanism of A. marina. Our results showed that 400 mM NaCl significantly reduced the plant height, leaf area, leaf biomass and photosynthesis of A. marina. In addition, 1565 differentially expressed genes were identified, of which 634 and 931 were up- and down-regulated. Based on Kyoto Encyclopedia of Genes and Genomes metabolic pathway enrichment analysis, we demonstrated that decreased gene expression, especially that of OEE1, PQL2, FDX3, ATPC, GAPDH, PRK, FBP and RPE, could explain the inhibited photosynthesis caused by salt treatment. Furthermore, the ability of A. marina to cope with 400 mM NaCl treatment was dependent on appropriate hormone signalling and potential sulfur-containing metabolites, such as hydrogen sulfide and cysteine biosynthesis. Overall, the present study provides a theoretical basis for the adaption of A. marina to saline habitats and a reference for studying the salt tolerance mechanism of other mangrove plants.
Background
Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that ...immunotherapy combined with antiangiogenic therapy is well‐tolerated and shows good antitumor activity. However, the efficacy of this combination as a later‐line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third‐ or further‐line therapy in stage IV non‐small cell lung cancer (NSCLC) patients with ECOG PS 2.
Methods
In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed.
Results
Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow‐up of 10.5 months (range: 0.7–23.7), the median PFS was 5.5 months (95% confidence interval CI: 3.8–7.3) and the median OS was 10.5 months (95% CI: 11.2–13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3–4 treatment‐related adverse events were hepatic dysfunction (6 10%), hypertension (5 8%), and hypothyroidism (3 5%). There were no treatment‐related deaths.
Conclusions
Third‐ or further‐line immunotherapy combined with antiangiogenic therapy is well‐tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large‐scale prospective studies are required to confirm the clinical benefits of this combination therapy.
A complex composed of presenilin (PS), nicastrin, PEN-2, and APH-1 is absolutely required for γ-secretase activity in vivo. Evidence has emerged to suggest a role for PS as the catalytic subunit of ...γ-secretase, but it has not been established that PS is catalytically active in the absence of associated subunits. We now report that bacterially synthesized, recombinant PS (rPS) reconstituted into liposomes exhibits γ-secretase activity. Moreover, an rPS mutant that lacks a catalytic aspartate residue neither exhibits reconstituted γ-secretase activity nor interacts with a transition-state γ-secretase inhibitor. Importantly, we demonstrate that rPS harboring mutations that cause early onset familial Alzheimer's disease (FAD) lead to elevations in the ratio of Aβ42 to Aβ40 peptides produced from a wild-type APP substrate and that rPS enhances the Aβ42/Aβ40 peptide ratio from FAD-linked mutant APP substrates, findings that are entirely consistent with the results obtained in in vivo settings. Thus, γ-secretase cleavage specificity is an inherent property of the polypeptide. Finally, we demonstrate that PEN2 is sufficient to promote the endoproteolysis of PS1 to generate the active form of γ-secretase. Thus, we conclusively establish that activated PS is catalytically competent and the bimolecular interaction of PS1 and PEN2 can convert the PS1 zymogen to an active protease.
Comprehensive Summary
The tribe Delphineae, comprising two genera, Aconitum L. and Delphinium L., is the richest source of bioactive diterpenoid alkaloids (DAs), while their highly similar chemical ...structures create a major challenge for dereplication from complex mixture. To solve the inefficient discovery process of natural DAs, a novel dereplication strategy based on pattern recognition of specific heteronuclear multiple bond correlation (HMBC) signals has been established in this study. This strategy utilized the diagnostic signals in the HMBC spectra of C19‐DAs, which could indicate the structural categories. The newly designed software MatchNat allowed in silico recognition of C19‐DA types. The developed dereplication system was demonstrated to be a practical strategy to dereplicate a variety of natural products from two Delphineae plants, including Aconitum vilmorinianum Kom. and Delphinium pachycentrum Hemsl. Known compounds could be rapidly recognized from the mixture, and novel DAs were found with the aid of MatchNat. Consequently, targeted isolation led to the explosive discovery of a series of novel DAs. This dereplication system has the potential to be adopted for dereplication of any other class of natural products and has shown promising application as a complementary tool in the nuclear magnetic resonance analysis of traditional Chinese medicines.
A novel 2D NMR‐based dereplication strategy MatchNat has been established to dereplicate natural products from two Delphineae plants, which led to the discovery of six novel diterpenoid alkaloids pachycentines A—F.
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